Search PubMed⌕ Search

Biomedical subjects

X L Yang

Publications and source records attributed to X L Yang.

At least 73 records · Page 4Linked to original sources

[Effect of endothelin-1 injected into rostral ventrolateral medulla on cardiovascular responses in cats].

AIM: To study the effect of endothelin-1 (ET-1) in the rostral ventrolateral medulla (rVLM) on cardiovascular responses in cats. METHODS: The stereotatic technique and microinjection method were used. RESULTS: ET-1 (4 mumol.L-1 0.5 microL) microinjected into rVLM induced mean arterial pressure (MAP) increasing (3.7 +/- 1.3) kPa, heart rate (HR) accelerating (29 +/- 7) beats.min-1, and renal nerve activity (RNA) intensifying 45% +/- 10%. The effects were dose-dependent. Before and after bilateral vagotomy, there was no significant difference in the reaction of MAP, HR, and RNA. After intravenous injection with phentolamine (5 mg.kg-1, alpha-blocker), ET-1 did not induce significant change of MAP. ET-1 raised the content of peripheral plasma argipressin (Arg) from (12.4 +/- 6.5) to (70.3 +/- 24.2) ng.L-1 with radioimmunoassay, and showed a correlation with MAP changes. ET-1 induced heart rhythm disorder (HRhD) in acute myocardiac ischemia, the occur time of HRhD was (4.8 +/- 2.9) min, and the score was 4.4 +/- 1.6, and it was significantly different from control. CONCLUSION: ET-1 microinjected into rVLM could involve with control regulation of cardiovascular and sympathetic nerve activity.

Animals↗

[Glycine modulates the ERG b-waves and ON-type bipolar cells in carp retina].

In the present work we investigated the effects of glycine on the electroretinograms (ERG) and light responses of ON-type bipolar cells under dark- and light-adapted conditions in superfused, isolated crucian carp retinas. It was revealed that application of 4 mmol/L glycine significantly suppressed the b-waves and the responses of ON-type bipolar cells and the effects were blocked by co-application of 20 mumol/L strychnine. In addition, glycine had no apparent action on the PIII component (photoreceptor potential) isolated by application of 3 mmol/L glutamate. These results suggest that glycine may act on bipolar cells directly and thus modulate the activity of the ON pathway in the retina.

Animals↗

[Response kinetics of GABA receptors and their functional significance].

It is an important issue whether and how the response kinetics, including activation, desensitization and deactivation, of gamma-aminobutyric acid (GABA) receptors plays roles in rapid inhibitory postsynaptic transmission. With the development of molecular biology, and the use of patch clamp techniques and rapid solution changers, the structural basis, underlying mechanisms at single channel level and functional roles of the characteristics of GABA receptors have been fully explored. It is revealed that the response kinetics of GABA receptors plays a crucial role in modulating inhibitory postsynaptic currents and has a great importance for rapid inhibitory synaptic transmission.

Animals↗

Strong synergism between GABA(A) and glycine receptors on isolated carp third-order neurons.

A strong synergistic interaction between the bicuculline-sensitive GABA receptor (GABA(A) receptor) and the strychnine-sensitive glycine receptor was observed in third-order neurons acutely isolated from crucian carp retina, with the use of the whole-cell patch-clamp recording technique. In 58 of 153 cells, 10 microM GABA or glycine separately applied to amacrine/ganglion cells failed to induce any responses or only induced small currents (<20 pA), while co-application of these two chemicals resulted in much larger responses (403.05+/-319.98 pA). The current induced by the co-application was mediated by chloride channels, and both GABA(A) and glycine receptors were involved in the potentiation. The underlying mechanisms of this interaction and its possible physiological role are discussed.

Animals↗

GABA modulates color-opponent bipolar cells in carp retina.

In the present work, the effects of gamma-aminobutyric acid (GABA) were examined while recording intracellularly from color-opponent bipolar cells in the isolated, superfused carp retina. Bath-applied GABA differentially suppressed light responses of R/G cells, which depolarized and hyperpolarized, respectively, in response to red and green flashes, and G/R cells, which showed the opposite responses. In either R/G or G/R cells, the response driven by input from red cones was invariably suppressed to a greater extent. Such effects of GABA were completely blocked by picrotoxin, but only partially by bicuculline, suggesting that the GABAC receptor, in addition to the GABAA receptor, may also be involved. It is postulated that GABA modulates the color-opponent bipolar cells either through activating GABA receptors on these cells directly or those on cone terminals indirectly.

Action Potentials↗

Restoration of holoceruloplasmin synthesis in LEC rat after infusion of recombinant adenovirus bearing WND cDNA.

Wilson's disease, an autosomal recessive disorder, is characterized by the excessive accumulation of copper in the liver. WND (ATP7B) gene, which encodes a putative copper transporting P-type ATPase, is defective in the patients. To investigate the in vivo function of WND protein as well as its intracellular localization, WND cDNA was introduced to the Long-Evans Cinnamon rat, known as a rodent model for Wilson's disease, by recombinant adenovirus-mediated gene delivery. An immunofluorescent study and a subcellular fractionation study revealed the transgene expression in liver and its localization to the Golgi apparatus. Moreover, since the synthesis of holoceruloplasmin is disturbed in the Long-Evans Cinnamon rat, the plasma level of holoceruloplasmin, oxidase-active and copper-bound form, was examined to evaluate the function of WND protein with respect to the copper transport. Consequently, the appearance of holoceruloplasmin in plasma was confirmed by Western blot analysis and plasma measurements for the oxidase activity and the copper content. These findings indicate that introduced WND protein may function in the copper transport coupled with the synthesis of ceruloplasmin and that the Golgi apparatus is the likely site for WND protein to manifest its function.

Adenosine Triphosphatases↗

Structural studies of a stable parallel-stranded DNA duplex incorporating isoguanine:cytosine and isocytosine:guanine basepairs by nuclear magnetic resonance spectroscopy.

Isoguanine (2-hydroxyladenine) is a product of oxidative damage to DNA and has been shown to cause mutation. It is also a potent inducer of parallel-stranded DNA duplex structure. The structure of the parallel-stranded DNA duplex (PS-duplex) 5'-d(TiGiCAiCiGiGAiCT) + 5'-d(ACGTGCCTGA), containing the isoguanine (iG) and 5-methyl-isocytosine (iC) bases, has been determined by NMR refinement. All imino protons associated with the iG:C, G:iC, and A:T (except the two terminal A:T) basepairs are observed at 2 degrees C, consistent with the formation of a stable duplex suggested by the earlier Tm measurements [Sugiyama, H., S. Ikeda, and I. Saito. 1996. J. Am. Chem. Soc. 118:9994-9995]. All basepairs are in the reverse Watson-Crick configuration. The structural characteristics of the refined PS-duplex are different from those of B-DNA. The PS duplex has two grooves with similar width (7.0 A) and depth (7.7 A), in contrast to the two distinct grooves (major groove width 11.7 A, depth 8.5 A, and minor groove width 5.7 A, depth 7.5 A) of B-DNA. The resonances of the amino protons of iG and C are clearly resolved and observable, but those of the G and iC are very broad and difficult to observe. Several intercalators with different complexities, including ethidium, daunorubicin, and nogalamycin, have been used to probe the flexibility of the backbone of the (iG, iC)-containing PS-duplex. All of them produce drug-induced UV/vis spectra identical to their respective spectra when bound to B-DNA, suggesting that those drugs bind to the (iG, iC)-containing PS-duplex using similar intercalation processes. The results may be useful in the design of intercalator-conjugated oligonucleotides for antisense applications. The study presented in this paper augments our understanding of a growing number of parallel-stranded DNA structures, including the G-quartet, the i-motif, and the unusual homo basepaired parallel-stranded double helix. Their possible relevance is discussed.

Base Pairing↗

Desensitization of AMPA receptors on horizontal cells isolated from crucian carp retina.

In horizontal cells freshly dissociated from crucian carp (Carassius auratus) retina, we recorded the whole-cell responses to rapid application of glutamate, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainate. Currents induced by glutamate and AMPA, but not by kainate, usually showed extremely rapid desensitization. 1-(4-aminophenyl)-3-methylcarbamyl- 4-methyl-7,8-methylenedioxy-3,4-dihydro-5H-2,3-benzodiazepine (GYKI 53655), a selective AMPA receptor antagonist, was found to completely block glutamate- and kainate-induced currents, which were supposed to be mediated by activation of AMPA receptors. We further extensively studied the kinetics of desensitization of glutamate- and AMPA-induced currents in horizontal cells. The time constants for decay of whole-cell currents induced by glutamate and AMPA were 1.9 and 1.4 ms, respectively, and the equilibrium responses to glutamate and AMPA at concentrations over 1 mM were invariably less than 10% of the corresponding peak responses. We have determined the values of EC50 for glutamate and AMPA as 1.08 and 1.05 mM, respectively, which are nearly 100-fold higher than that reported previously. Dose dependence of desensitization was also investigated and the glutamate concentration for a half desensitization was 26 microM, much lower than the EC50. Furthermore, kainate and AMPA interacted at AMPA receptors of horizontal cells in a dual competitive manner: the response to kainate of low concentration (10 microM) was potentiated by the addition of 300 microM AMPA, while the responses induced by kainate of relatively higher doses (300 microM or more) were reduced. We conclude that crucian carp horizontal cells may exclusively express the AMPA subtype of glutamate receptors, which is characterized by extremely rapid desensitization.

Animals↗

User acceptability of a female condom (Reality) in Shanghai.

Thirty married couples evaluated the Reality female condom on questionnaires about its acceptability for 300 acts of coitus (10 per couple). An analysis of the summary questionnaires showed: 90% of couples considered the female condom an acceptable method and 87% felt it was a good contraceptive device; the majority of couples (87%) found it easy to use; and 80% of females and 73% of males reported that, in comparison with the male condom, the effect on sexual pleasure was either improved or no different. A little more than half of the couples (55%) preferred it to male condoms. To look at the learning curve effect, an additional analysis was completed by pooling the first 5 applications of each user and comparing the results with the pooled results of the second 5 uses. All the findings suggest that a certain proportion of couples of childbearing age will choose the Reality female condom for contraception if it enters into the Chinese market. As a new contraceptive barrier device, the female condom may require a certain amount of education and awareness before it will be fully recognized as an important option to help prevent pregnancy as well as sexually transmitted infections.

Adult↗

Nonsteroidal antiinflammatory drugs could reverse Helicobacter pylori-induced apoptosis and proliferation in gastric epithelial cells.

It remains controversial whether the harmful effects of Helicobacter pylori (Hp) and nonsteroidal antiinflammatory drugs (NSAIDs) are additive. We studied the effects of Hp (virulent and nonvirulent strains) and NSAIDs, alone or in combination, on apoptosis and proliferation of gastric epithelial cells in nonulcer dyspepsia (NUD) patients. Forty-four (25 Hp-positive and 19 Hp-negative) consecutive Chinese NUD patients with rheumatoid arthritis who had taken continuously NSAIDs for more than three months were recruited for this study. Another 41 (20 Hp-positive and 21 Hp-negative) NUD patients not on any NSAIDs were included as controls. All patients underwent a gastroscopy examination and gastric biopsies. Hp infection was confirmed by CLOtest, anti-Hp ELISA, and [13C]urea breath test. The CagA status was determined by the anti-CagA antibody assay. The degree of gastritis, apoptosis, and proliferation indices were determined with H&E staining, terminal uridine deoxynucleotidyl nick end-labeling (TUNEL), and proliferating cell nuclear antigen (PCNA) immunostaining methods, respectively. A significantly higher apoptosis was observed in subjects who had Hp infection or had been consuming NSAIDs when compared with the controls. Unlike NSAID-treated subjects, patients with Hp infection were shown to have significantly enhanced cell proliferation. However, the increased apoptosis and proliferation in Hp-positive subjects were reversed by also taking NSAIDs. No correlation was found between apoptosis and proliferation in all the study groups. There was no association found between CagA expression or degree of gastritis with cell proliferation or apoptosis. It was demonstrated at the cellular level that NSAIDs could abrogate apoptosis or proliferation effects induced by Hp. Furthermore, the latter effects appeared not to be influenced by the virulent nature of the Hp strains.

Anti-Inflammatory Agents, Non-Steroidal↗

[Müller cells and retinal function].

Müller cells are the principal neuroglia cells in the retina. Recently, a lot of evidence indicate that there exist two-way communications between Müller cells and retinal neurons. Müller cells may modulate neuronal activity in the retina either indirectly through modifying neuronal microenvironment or directly by controlling the concentration of neuroactive substances in extracellular space, in addition to their general supporting and nourishing roles. Müller cells thereby play an important role in retinal function.

Humans↗

Two forms of Wilson disease protein produced by alternative splicing are localized in distinct cellular compartments.

Copper is an essential trace element in prokaryotes and eukaryotes and is strictly regulated by biological mechanisms. Menkes and Wilson diseases are human disorders that arise from disruption of the normal process of copper export from the cytosol to the extracellular environment. Recently a gene for Wilson disease (WD)(also named the ATP7B gene) was cloned. This gene encodes a copper transporter of the P-type ATPase. We prepared monoclonal and polyclonal anti-(WD protein) antibodies and characterized the full-length WD protein as well as a shorter form that is produced by alternative splicing in the human brain. We found that the WD protein is localized mainly in the Golgi apparatus, whereas the shorter form is present in the cytosol. These results suggest that the alternative WD proteins act as key regulators of copper metabolism, perhaps by performing distinct roles in the intracellular transport and export of copper.

Adenosine Triphosphatases↗

OFF pathway is preferentially suppressed by the activation of GABA(A) receptors in carp retina.

This study examines the effect of gamma-aminobutyric acid (GABA) on the ON and OFF pathways in isolated, superfused carp retina. In most (76%) of amacrine cells bath-applied GABA preferentially suppressed the OFF response. The effect of GABA was blocked by bicuculline. Baclofen did not cause a similar effect. Furthermore, GABA produced a substantial suppression of the OFF bipolar cell response. We conclude that the preferential suppression of the OFF pathway may be due to a presynaptic inhibition mediated via GABA(A) receptors at the terminals of OFF bipolar cells.

Animals↗

Isolation of the mouse (MFH-1) and human (FKHL 14) mesenchyme fork head-1 genes reveals conservation of their gene and protein structures.

The very recently found evolutionarily conserved DNA-binding domain of 100 amino acids, termed the fork head domain, emerged from a sequence comparison of the rat hepatocyte transcription factor HNF-3 alpha and the homeotic gene fork head of Drosophila. We previously isolated a new member of this family, the mesenchyme fork head-1 (MFH-1) gene, which is expressed in developing mesenchyme. Here we describe the isolation of the mouse (MFH-1) and human (FKHL14) chromosomal MFH-1 genes and the determination of the gene and protein structures of MFH-1. We found that the MFH-1 gene has no introns and that the identity of the amino acid sequences of mouse and human MFH-1 proteins is 94%. We also investigated the transcriptional activity of the mouse and human MFH-1 proteins and found that both proteins act as positive transactivators.

Amino Acid Sequence↗

Desensitizing GABAC receptors on carp retinal bipolar cells.

Bicuculline- and baclofen-insensitive GABA receptors (GABAC receptors) on bipolar cells acutely dissociated from carp retina were investigated with using the whole-cell patch-clamp recording technique. The currents of these cells mediated by GABAC receptors showed striking desensitization, even at low concentrations of GABA. Both the time constant tau of the GABAC current decay and the extent of desensitization were significantly different from that of GABAC receptors previously observed in other retinas and elsewhere in the CNS, suggesting that the GABAC receptors of carp bipolar cells might be distinct in intracellular mechanisms and subunit composition.

Animals↗

Structural analysis of Z-Z DNA junctions with A:A and T:T mismatched base pairs by NMR.

Left-handed Z-DNA structure is favored by the alternating (dC-dG)n sequence. Many Z-potentiating sequences are found in genome and they often do not have a perfect alternating (dC-dG)n sequence. When a single base pair is removed from the alternating (dC-dG)n sequence, a Z-Z junction is created. A Z-Z junction is energetically less favorable by 3.5 kcal/mol than a perfect Z-DNA sequence. We designed special sequences to probe the structural perturbation at the Z-Z junction. Four DNA oligomers, d(*CG*CGT*CG*CG) and d(*CG*CGA*CG*CG) (*C = C or br5C), have been synthesized and analyzed by NMR. The two br5C-modified DNA nonamers are in the Z-DNA conformation in 50% methanol solution. The T and the A nucleotides are in the anti and syn conformation, respectively, in the two br5C nonamers. The NOE-restrained molecular dynamics refinement demonstrated that T-T and A-A bases in the two Z-DNA duplexes are dynamic and adopt a range of conformations. Mixing the br5C-d(*CG*CGT*CG*CG) and br5C-d(*CG*CGA*CG*CG) nonamers together converts a fraction of the two nonamer populations into a hetero duplex as evident from the presence of the imino proton (at 13.70 ppm) of an A:T base pair. A model has been generated for the br5C-d(*CG*CGT*CG*CG)+br5C-d(*CG*CGA*CG*CG) duplex which incorporates a Z-Z junction. Previous biophysical and biochemical data associated with the Z-Z junction are discussed in the context of the present model.

Adenine↗

Unexpected genetic and structural relationships of a long-forgotten flavoenzyme to NAD(P)H:quinone reductase (DT-diaphorase)

A mammalian cytosolic FAD-dependent enzyme that catalyzes the reduction of quinones by N-ribosyl- and N-alkyldihydronicotinamides, but not by NADH, NADPH, or NMNH (reduced nicotinamide mononucleotide), was isolated from bovine kidney more than 30 years ago [S. Liao, J. T. Dulaney and H. G. Williams-Ashman (1962) J. Biol. Chem. 237, 2981-2987]. This enzyme is designated here as quinone reductase type 2 (QR2). Bovine QR2 is a homodimer that migrates on SDS/PAGE at approximately 22 kDa. Three tryptic peptides of bovine QR2 (representing 39 amino acids) showed 43% identity to human NAD(P)H:quinone reductase (DT-diaphorase; EC 1.6.99.2), here designated QR1 and 82% identity to a related human cDNA clone [called hNQO2 by A. K. Jaiswal, P. Burnett, M. Adesnik and O. W. McBride (1990) Biochemistry 29, 1899-1906], and designated here as hQR2. The protein encoded by the latter cDNA did not show QR activity when tested with conventional nicotinamide nucleotides. The unexpected high homology between the old flavoenzyme and hQR2 prompted us to clone and overexpress hQR2. The properties of hQR2 were identical to those of the flavoenzyme described by S. Liao and H. G. Williams-Ashman, thus establishing their genetic identity. Recombinant human QR2: (i) reacts with N-ribosyl- and N-alkyldihydronicotinamides, but not with NADH, NADPH, or NMNH; (ii) is very weakly inhibited by dicumarol or Cibacron blue; (iii) is very potently inhibited by benzo[a]pyrene. The x-ray crystal structure of rat QR1 shows that the 43 amino acid C-terminal tail of QR1 provides the binding site for the hydrophilic portions of NADH and NADPH. In the absence of this binding site in QR2, the enzyme retains the essential catalytic machinery, including affinity for FAD, but cannot bind phosphorylated hydride donors.

Amino Acid Sequence↗

Response sensitivity and voltage gain of the rod- and cone-bipolar cell synapses in dark-adapted tiger salamander retina.

Response sensitivity and voltage gain of the rod- and cone-bipolar cell synapses in dark-adapted tiger salamander retina. J. Neurophysiol. 78: 2662-2673, 1997. Rods, cones, and bipolar cells were recorded in superfused, flat-mounted isolated retinas of the larval tiger salamander, Ambystoma tigrinum, under dark-adapted conditions. Voltage responses of 24 rods, 15 cones, and 41 bipolar cells in dark-adapted retinas to 500 nm light steps of various intensities were listed and fitted with hyperbolic functions, and their step sensitivities and relative sensitivities (log sigma) were estimated. In the linear response-intensity ranges, the step sensitivity of rods, SS(rod), is -1.0 mV photon-1 micron2 s or 0.034 mV Rh*-1 s rod and that of the cones, SS(cone), is approximately 0. 00146 mV photon-1 micron2 s or 0.000048 mV Rh*-1 s rod. The rod and cone responses were relatively homogenous with little variations in response amplitude and sensitivity. In contrast, bipolar cell responses were heterogenous with large variations in response amplitude and sensitivity. The maximum response amplitude of bipolar cells varied from 5 to 25 mV, and the relative response sensitivity (log sigma) varied >6 log units (-8.11 to -2.32). The step sensitivity of bipolar cells in the linear response-intensity range varied from 0.0000438 to 51.82 mV photon-1 micron2 s. Bipolar cells in dark-adapted tiger salamander retinas fell into two groups according to their relative sensitivities with very few cells falling in the intermediate light intensity region. The mixed bipolar cells (DBCM and HBCM) exhibited relative response sensitivity ranged from -8.11 to -5.54, and step sensitivity ranged from 1.22 to 51.82 mV photon-1 micron2 s. The cone-driven bipolar cells (DBCC and HBCC) exhibited relative response sensitivity ranged from -3.45 to -2.32, and step sensitivity ranged from 0.0000438 to 0. 00201 mV photon-1 micron2 sec. The chord voltage gain of the rod-DBCM or rod-HBCM synapses near the rod dark membrane potential ranged from 1.14 to 48.43 and that of the cone-DBCC or cone-HBCC synaptic gain near the cone dark membrane potential ranged from 0.03 to 1.38. The highest voltage gains were found near the rod or cone dark membrane potentials. By the use of linear subtraction method, we studied the synaptic inputs from cones to five mixed bipolar cells, and the voltage gains of the cone synapses in each of the bipolar cells were very close to the voltage gain of the rod synapses. This result suggests that although the responses of mixed bipolar cells are mediated mainly by rods when lights of short and medium wavelengths are used, their responses to long wavelength lights (>650 nm) are mediated by both rods and cones with comparable synaptic gains. Functional roles of the mixed and cone-driven bipolar cells in information processing in dark-adapted retinas are discussed.

Adaptation, Ocular↗